Clinical Study on the Treatment of Elevated Total Bilirubin in Primary Biliary Cholangitis With Baobao Dan Capsule

Clinical Study on the Treatment of Elevated Total Bilirubin in Primary Biliary Cholangitis With Baobao Dan Capsule

1. Explore the effect of Babaodan Capsule on the serum total bilirubin level of primary biliary cholangitis patients with elevated total serum bilirubin;
2. To observe the positive intervention effect of Babaodan Capsule on the clinical symptoms of primary biliary cholangitis patients with elevated total bilirubin.

1. Primary objective: to investigate the effect of Baobao Dan capsule on serum total bilirubin levels in patients with primary biliary cholangitis with elevated total serum bilirubin.
2. Secondary objective: to observe the effects of Babaodan Capsule on the following aspects in patients with primary biliary cholangitis with elevated total bilirubin:

(1) Other indicators of liver function: ALP, GGT, AST, ALT, TBA, TBil, DBil, IBil; (2) Itching and fatigue symptom scores; (3) Biochemical response rate; (4) Histologic changes; (5) Changes in immunologic indices (serum IgM, IgG, IgA, autoantibodies AMA/AMA-M2 and anti-gp210 antibody, anti-sp100 antibody); (6) Adverse events and safety evaluation.

Inclusion Criteria:

• 1. meets the diagnostic criteria for primary biliary cholangitis (PBC) in the Diagnostic and Therapeutic Guidelines for Primary Biliary Cholangitis (2021), i.e., meets at least 2 out of the following 3 criteria: (i) Biochemical evidence of cholestasis, i.e., elevated ALP and GGT, and imaging studies that exclude extrahepatic or intrahepatic biliary obstruction; (ii) Anti-mitochondrial antibody (AMA) or AMA-M2 positivity or, if AMA negative, PBC-specific antibody (anti-GP210 and/or anti-SP100) positivity; (iii) Histologic evidence suggestive of non-purulent destructive cholangitis and interlobular bile duct destruction.
• 2. Male or female, ≥ 18 years of age and < 75 years of age;
• 3. ursodeoxycholic acid capsule (Yusuf) 10 ~15 mg/d for ≥6 months prior to screening and after screening enrollment, the therapeutic dose was maintained unchanged for the duration of the trial;
• 4. ALP ≥ 1.67 x ULN;
• 5. liver function tests no less than 2 times in the last 3 months, and total bilirubin in liver function tests before enrollment and in the last 3 months are in accordance with the following: 1 × ULN < TBil ≤ 5 × ULN;
• 6. Understand the content of the study, be willing to comply with the study protocol, and voluntarily sign the written informed consent.

Exclusion Criteria.

• 1. Combination of or history of other liver diseases, including: (1) hepatitis C virus (HCV) infection; (2) hepatitis B virus (HBV) infection; (3) primary sclerosing cholangitis (PSC); (4) alcoholic liver disease; (5) autoimmune hepatitis (AIH) or overlapping autoimmune liver disease; (6) nonalcoholic steatohepatitis (NASH); (7) drug-induced liver injury; (8) extrahepatic biliary obstruction; (9) Gilbert's syndrome; (10) suspected or diagnosed primary liver cancer; (11) suspected or confirmed primary liver cancer; and (12) extrahepatic biliary obstruction; ⑨ Gilbert's syndrome; ⑩ suspected or confirmed primary liver cancer;
• 2. Presence of clinical complications of PBC, including but not limited to: (i) history of liver transplantation, pending liver transplantation, or current Model for End-Stage Liver Disease (MELD) score ≥ 15; (ii) portal hypertension with complications, including gastric or large esophageal varices, refractory or diuretic-resistant ascites, history of variceal hemorrhage, history of variceal treatment such as use of β-blockers, endoscopic tissue adhesive injections or ligatures, transjugular portacaval shunts, or hepatic encephalopathy; (iii) cirrhosis with Complications, including spontaneous bacterial peritonitis, hepatocellular carcinoma; 4. Hepatorenal syndrome (type I or II) or screening serum creatinine (Cr) ≥ 1.5 x ULN and serum creatinine clearance < 60 mL/min;
• 3. Hepatic function Child-Pugh classification grade B/C;
• 4. ALT ≥ 5 × ULN and/or AST ≥ 5 × ULN;
• 5. ALP > 10 × ULN;
• 6. patients with pruritus with severe itching or requiring systemic medication (e.g., bile acid sequestrants or rifampicin, etc.) within 2 months prior to enrollment
• 7. use of the following medications within 3 months prior to enrollment: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, hexacosanol, dicyclomine, simethicone, ximethicone; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; and hepatotoxic medications (including alpha-methyldopa, valproate, isoniazid, furosemide, etc.);
• 8. use of the following medications within 12 months prior to enrollment and throughout the trial: antibodies or immunotherapies against interleukins or other cytokines or chemokines;
• 9. having or having had a previous cardiac arrhythmia requiring clinical intervention that may affect survival during the trial; or pre-treatment QT prolongation or QTc intervals ≥470ms in men and ≥480ms in women
• 10. pregnant, planning pregnancy, breastfeeding women, women of childbearing potential who do not wish to use effective contraception (≥1 effective method of contraception e.g., condom, hormonal contraceptive pill, intrauterine device), or male subjects who do not wish to use contraception during the trial period and up to 30 days after the last dose of study medication
• 11. patients with co-infections of infectious diseases such as HIV, syphilis, and neo-coronavirus;
• 12. the presence of any other disease or condition that interferes with the absorption, distribution, metabolism, or excretion of the drug (e.g., patients with inflammatory bowel disease or those who have undergone gastric bypass surgery);
• 13. any other disease that is not well controlled or for which the need for the drug is expected to change during the trial;
• 14. persons with a suspected or confirmed history of alcohol or drug abuse within 1 year prior to screening;
• 15. incapacitated or restricted persons;
• 16. subjects who have been enrolled in another study within 30 days prior to Screening
• 17. mentally unstable or incapacitated persons for whom the validity of informed consent or compliance with the trial is uncertain;
• 18. has had a malignant tumor in the last 5 years, with or without treatment and with or without evidence of local recurrence or metastasis;
• 19. the patient has taken Babao Dan capsule within 1 month prior to the trial;
• 20. who, in the opinion of the investigator, should not participate in the trial.